Patient Breathing Modeling

ABSTRACT

A method of accounting for the movement of the lungs during an endoscopic procedure such that a previously acquired image may be dynamically registered with a display showing the position of a locatable guide. After an initial image set is acquired, an area of interest is identified and the movement thereof due to breathing is mathematically modeled. Patient movement sensors are then used to provide information on the patient&#39;s breathing patterns. This information is entered into the mathematical model in order to update the registration between the image set and a display showing the position of the locatable guide.

RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application Ser.No. 60/948,640 filed Jul. 9, 2007 entitled Patient Breathing Modeling;and U.S. Provisional Application Ser. No. 61/043,987 filed Apr. 10, 2008entitled Patient Breathing Modeling, all of which are herebyincorporated by reference.

BACKGROUND OF THE INVENTION

The method of the present invention relates generally to the accurateregistration of a detected sensor located in moving lungs to a staticimage of the lungs. The evolution of procedures using less-invasivescopes has resulted in the development of sensors that can be attachedto end of an endoscope and used to determine the three-dimensionallocation and orientation of the end of the endoscope. Examples of suchsensor technology is shown and described in various patents and patentpublications including U.S. Pat. No. 6,188,355 to Gilboa, U.S. Pat. No.6,380,732 to Gilboa, U.S. Pat. No. 6,593,884 to Gilboa et al., U.S. Pat.No. 6,615,155 to Gilboa, 6,833,814 to Gilboa et al., U.S. Pat. No.6,947,788 to Gilboa et al., each of which is incorporated herein in itsentirety. Additionally, there are many other technologies (lasertechnology, ultrasound technology, etc.) directed toward for locating amedical tool (catheter, endoscope, needle) inside the human lungs.

One problem that arises while using these localization methods is that,in order to provide information that is useful to a physician, a displaymust be used that shows a representation of the tool superimposed on animage of the lungs. If a static image of the lungs is used, the tool,which is moving with the lungs as the patient breathes, appears to floatin and out of the airways in the preliminary, relatively static image.Accurately matching the position of the sensor in the lungs to an imageof the lungs is achieved by “registration.” Ideally, the desired resultof registration would involve matching the tool representation to areal-time, dynamic image of the lungs. However, this would requireconstant exposure to X-ray radiation by both the patient and the medicalstaff during while performing the dynamic registration.

One approach at solving this problem is described in U.S. Pat. No.7,117,026 to Shao et al., which is incorporated by reference herein inits entirety. Shao is directed to reconciling a dynamic, PET imagingdata set with a static CT imaging data set. Shao accomplishes this bymerely morphing (stretching or distorting) the image sets together.Doing so does not necessarily improve the accuracy of the real-time databeing displayed because at least one of the data sets is beingdistorted. Rather, this approach merely makes the display appear to bemore accurate. Moreover, PET requires prolonged exposure to radioactiveimaging agents.

Another approach at solving this problem is described in U.S. PatentPublication No. 2003/0185346 to Vilsmeier. Vilsmeier is directed toavoiding costly CT scans by building a generic model of various areas ofthe body using a compilation of data from various patients, and thenadapting that generic model to a specific patient. This idea certainlyreduces costs and exposure to radiation, however it necessarilycompromises image accuracy. Moreover, though the anatomy of the tracheaand upper bronchial anatomy is very similar in most people, the lowerbronchi become very patient-specific. It is in these lower bronchi whereaccurate information is most important. Finally, Vilsmeier does notaddress developing a dynamic model. Not only are the lower bronchi morepatient-specific, they move more. So even if one where to use theVilsmeier model to create a dynamic lung simulation, the lack ofaccuracy in the lower bronchi would not solve the problem the presentinvention addresses.

One reference that discusses the development of a generic model andbegins to analyze the movement vectors for a breathing cycle is entitled“Development of a Dynamic Model for the Lung Lobes and Airway Tree inthe NCAT Phantom” and is written by Garrity et al. This reference waspublished in 2002 as part of the Nuclear Science Symposium ConferenceRecord, and appears in IEEE Vol. 3, pp. 1858-1862. This reference isincorporated herein in its entirety. It describes an algorithm thatfills an empty outline of a simulated lung lobe with a virtual bronchialtree. The bronchial tree simulates movement due to breathing and cardiacrhythms. Because the model is completely simulated, it is useful forstudying lung movement and the effects of tumor, but it would not haveapplication during a procedure on an actual patient. Additionally, thereference discusses movement vectors within the lungs, but it does notfind a mathematical relationship between these various vectors.

There is thus an identified need for a representation of the lungs thatis more representative of a breathing patient's lungs than a static,previously acquired image, but does not result in an increased exposureto radiation.

SUMMARY OF THE INVENTION

The method of the present invention provides a representative modelingof the human lungs, based on statistical anatomical data, which can betailored to the size and shape of an individual patient. The method ofthe present invention also utilizes a compilation of statisticalanatomical data regarding lung movement in order to predict the movementof an individual patient's lungs during the breathing cycle.

Breathing causes the lungs to move cyclically. The movement varies byamplitude and direction during the breathing cycle from 5 mm to 30 mmdepending on such breathing characteristics as patient size, age,altitude, health, etc. In order to reduce the deviation this movementcauses between a living patient and a static image, lung movement ismodeled. Dynamic modeling, according to the present invention, is basedon a comparison of multiple CT data sets.

In one embodiment of the present invention, one or more static images,such as a CT data set, may be “brought to life” by applying amathematical model that predicts how a given point in the lungs willmove during the breathing cycle, based on a large sample of statisticaldata. The mathematical model is tied to one or more external positionsensors on the patient's chest. Hence, by monitoring the externalsensor(s), and applying the mathematical movement model, aninstantaneous position of a given point in the lungs can be predicted.The patient's breathing cycle and its parameters may alternatively bemonitored using internal sensors, or other devices such as spirometrydevices, for example.

In another embodiment, each data set will preferably include at leastone exhale scan and one inhale CT scan, acquired while the patient isholding an exhaled state or inhaled state, respectively. These scanswill then be used as the extreme positions of the patient's breathingcycle.

The aforementioned mathematical movement model is then used to fill inthe lung positions between the inhalation and exhalation points acquiredby the CT scans of the actual patient. Additionally, any scans taken ofthe patient's lungs in intermediate breathing positions could also beadded to the dynamic modeling set. Such acquired actual position datamay be used to validate or modify the mathematical model as appropriate.

Alternatively, instead of matching the patient's characteristics topreviously acquired CT scans of one or more other patients, the path agiven point in a lung travels between inhalation and exhalation can bedescribed mathematically and stored in a computer. The mathematicalequations of the movement can be tied to one or more marker positions,so as the patient breathes, the computer may calculate the correspondingposition of the point based on the position of the one or more markers.The computer can then implement the mathematical equations stored for aplurality of points to either create a dynamic representation of thelungs and present this to the user via a display, or synchronize thismovement with the real-time movement of the LG and present the LG asthough it were not moving cyclically, just advancing and turningaccording to its manipulation by the user. In other words, the computercan use the plurality of mathematical equations as a filter, applied tothe graphic display of the LG.

Example 1

Constantly measuring the point at which a patient is in the breathingcycle allows a corresponding CT scan, which is closer to the actualposition to the location of the sensor to be displayed over the sensorimage.

Example 2

The measured location of the tool can be corrected using the patientbreathing model. In this way the tool may be localized more correctlyinside the CT volume. And therefore any geometric model derived from theCT volume can be more accurately represented relative to the tool insidethe body.

Example 3

Using a well known technique called image warping, the CT Volume can bechanged dynamically using the patient breathing model and according tothe monitored phase of breathing cycle. This can be used to displayaugmented reality images to perform the simulation of dynamic X-Raymodalities such as fluoroscopy, dynamic CT, etc., to simulate thepatient physiology synchronized to the actual patient, study the tissuemovement relative to the inserted tools, and for other purposes as well.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a flowchart of one embodiment of the method of the presentinvention;

FIG. 2 is a flowchart of a second embodiment of the method of thepresent invention; and,

FIGS. 3-12 are graphs and charts showing the data results of experimentsconducted on seven patients using the methods of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

Referring now to the figures and first to FIG. 1, there is shown aflowchart that illustrates one embodiment 20 of the method of thepresent invention.

At 30 the patient characteristics are measured or determined. “Patientcharacteristics” is a term defined herein as any attribute of thepatient that will influence the position of his or her lungs during anygiven point in the breathing cycle. Patient characteristics include, butare not limited to patient size (lung size), lung shape, lung health,altitude, patient age, diaphragm size, and diaphragm health. Thoughaltitude is not intrinsic to any given patient, the elevation at which apatient is breathing impacts the depth and/or the frequency of thebreaths taken during the breathing cycle. Lung health relates to thelung capacity of a given patient and includes such factors as whetherthe patient smokes, whether the patient has an increased lung capacitydue to athletic training, whether the patient has a condition such ascystic fibrosis, etc. One skilled in the art will realize that somepatient characteristics are more determinative of lung position thanothers and that it may only be feasible to factor a few of the listedcharacteristics into the matching process described below. Moreover,which factors are most determinative will likely vary by patient. Manyof the characteristics can be measured using a CT scan performed priorto the procedure.

At 40 the patient is imaged using any imaging modality that shows thelungs or desired target area. Most likely, CT imaging will be used. TheCT imaging may be high definition CT and preferably a first image set istaken with the lungs full of air and a second image set is taken afterthe patient has fully exhaled. However, it is envisioned that a singleCT image set may be used if there is accurate data regarding how fullthe lungs are when the image is taken.

At 50 the images taken at 40 are reviewed and at least one area ofinterest (hereinafter “AOI”) is identified. Identifying an AOI willallow the focus to remain on applicable areas of the lungs and reducethe number of computations that have to be made in later steps.

At 60 it is determined where the patient position sensors should beplaced. The patient position sensors are sensors on the chest, sensorsin the lungs, or a device such as a spirometry device, that are used tomeasure the positions of key points on the patient's body in order todetermine where the patient is in the breathing cycle. The data fromthese sensors are not only used as an entering argument for the upcomingmathematical modeling step 70, but also to monitor the physical locationof the patient in order to register a real-time image (such as thatacquired to show the position of the locatable guide) to the CT scanimage(s).

At 70 a mathematical model is developed to describe the movement at oneor more points in the AOI(s) during the breathing cycle. Themathematical model uses data from the patient position sensors asentering arguments and the result of the solved algorithm is a threedimensional position of the point in question. Selecting more points ina given AOI will result in a better registration between a display ofthe locatable guide (LG) and the CT scan taken at 40. The mathematicalalgorithm used to develop the model may be obtained by collecting dataon a number of subjects in a study and relating the movement of givenpoints to the point in the breathing cycle in which the positions wereacquired. Alternatively, the mathematical algorithm may be developedusing computer simulated models, such as those described in theaforementioned Garrity et al. reference. Examples of algorithmsdeveloped for the present invention and proven useful throughexperimentation are described below.

At 80 the procedure begins on the patient. The patient movement sensorsare placed on or in the patient. The physician intubates the patient andthe LG is inserted and tracked. The CT scan from 40 is displayed andregistered to the superimposed LG display.

As the LG is being inserted, the location(s) of the patient locationsensors are constantly monitored and entered into the algorithm toprovide three dimensional location data on the AOI(s). This informationis then used at 90 to ensure that the display is modified such that theLG display maintains an accurate registration with the CT scan, despitethe movement of the lungs, which cause the LG to move.

There are at least three ways at 90 in which the data acquired from 80can be used to improve the registration between the LG display and theCT scan. These three examples are not to be considered exclusive, as oneskilled in the art will see the usefulness of the data acquired at 80and realize other ways to apply the data at 90 or subsequent steps.

Example 1. If multiple CT scans were acquired at 40, the data acquiredat 80 may be used to determine which CT scan most accurately depicts theconfiguration of the lungs and can thus be superimposed onto the LGdisplay.

Example 2. The measured location of the LG can be corrected using thedata acquired at 80. Rather than displaying the real-time data acquiredby the LG system, which represents the position of the LG in relation toa magnetic field filling the AOI, the real-time data is manipulated sothe LG appears in the correct location on the CT scan, which may bestatic or dynamic. In this way the tool may be localized more correctlyinside the CT volume. The geometric model derived from the CT volume canthus be more accurately represented relative to the tool inside thebody.

Example 3. Using a well-known technique called image warping, the CTVolume can be changed dynamically using the data acquired at 80 andaccording to the monitored phase of breathing cycle. This can be used todisplay augmented images to perform the simulation of dynamic X-Raymodalities such as fluoroscopy, dynamic CT, etc., to simulate thepatient physiology synchronized to the actual patient, study the tissuemovement relative to the inserted tools, and for other purposes as well.

Referring now to FIG. 2, there is shown a flowchart that illustratesanother embodiment 120 of the method of the present invention.

At 130 the patient characteristics are measured or determined. “Patientcharacteristics” is a term defined herein as any attribute of thepatient that will influence the position of his or her lungs during anygiven point in the breathing cycle. Patient characteristics include, butare not limited to patient size (lung size), lung shape, lung health,altitude, patient age, diaphragm size, and diaphragm health. Thoughaltitude is not intrinsic to any given patient, the elevation at which apatient is breathing impacts the depth and/or the frequency of thebreaths taken during the breathing cycle. Lung health relates to thelung capacity of a given patient and includes such factors as whetherthe patient smokes, whether the patient has an increased lung capacitydue to athletic training, whether the patient has a condition such ascystic fibrosis, etc. One skilled in the art will realize that somepatient characteristics are more determinative of lung position thanothers and that it may only be feasible to factor a few of the listedcharacteristics into the matching process described below. Moreover,which factors are most determinative will likely vary by patient. Manyof the characteristics can be measured using a CT scan performed priorto the procedure.

At 140 the patient is imaged using any imaging modality that shows thelungs or desired target area. Most likely, CT imaging will be used.Preferably a first image set is taken with the lungs full of air and asecond image set is taken after the patient has fully exhaled.

At 150 the patient is matched to an archived data set taken from a datalibrary. It is desirable to find an archived data set that matches thepatient's breathing cycle as closely as possible. In order to match adata set to the patient, the patient characteristics are used asmatching criteria. The specific characteristics that are used, and thenumber of different characteristics that are used, are largely dependenton the size of the data library. However, if the patient has anydistinguishing lung traits, such as a significantly reduced capacity dueto smoking, they should be given more weight than other,less-distinguishing traits when looking for a matching data set.

Alternatively, the inhaled and exhaled positions recorded and measuredusing CT scans could be used as the entering arguments for matching thepatient to a data set. If the inhaled and exhaled positions are closelymatched to a data set, it will be likely that the intermediate pointsbetween inhalation and exhalation will also match. However,considerations like patient size should still be considered to ensurethat the lung geometries are also matched.

At 160 a CT image set for the patient is generated. The closely-matcheddata set is either used alone, or if inhalation and exhalation CT scanshave been taken, they are added to the data set to improve the degree towhich the data set is matched to the actual patient geometry.

At 170 each image of the image set is assigned to a lung position, asmeasured by external or internal means. Because each of the images willbe displayed during the procedure at different times during thebreathing cycle, it is necessary to determine, in advance, when eachimage will be cued for display. There are at least two ways in whichthis may be done. First, the positions of sensors, such as externalsensors placed on the patient's chest, may be monitored throughout thebreathing cycle. Each image may be examined to determine a position ofthe lungs that is most closely matched to that particular image. Whenthe external sensors indicate a particular lung position, the image willbe changed to the most closely matched image. Second, an averagebreathing cycle may be measured to determine the inhaling period(defined herein as the amount of time between inhalation and exhalation)and the exhaling period (defined herein as the amount of time betweenexhalation and inhalation). At the beginning of the inhaling period itwill be known to display the inhalation image taken at 150. At theexhalation point, it will be known to display the exhalation image takenat 150. The measured periods may be divided by the number ofintermediate images in the data set to determine an interval time. Theimages will then be changed each interval.

At 180 the actual procedure begins. During the procedure, the lungposition is monitored. If the first method at 170 was used, sensors onthe chest, sensors in the lungs, or a device such as a spirometry deviceis used to determine when the images shall be displayed at 190 to mostaccurately represent the actual lungs. If the second method at 170 wasused, the breathing cycle will be monitored using any of theaforementioned sensors or devices, to update the average inhaling andexhaling periods of the breathing cycle. At 190, the images will bechanged according to the constantly-updated intervals.

One skilled in the art will realize that the second method at 160 avoidsthe process of examining each individual image of the data set to assignit to a point in the breathing cycle. However, one skilled in the artwill also see the potentially improved accuracy of the first method.Because an unconscious patient does not breathe at a constant depth, theinhalation points and exhalation points will vary during each breathingcycle. If the first method is used and the lung positions are monitoredto determine which image to display at 190, during times of shallowbreathing, the inhalation and exhalation scans may never be displayed.This is because during times of shallow breathing, the sensors willnever measure a lung position that triggers the display of the scanstaken at 140. However, if the second method is used, the extremes areshown each cycle. The only variance will be the frequency of the imagechanges.

In order to combine the advantages of first and second methods, oneembodiment of step 170 maintains a constant image interval duringshallow breaths but ends the progression of images shown from exhalationpoint when it is determined that the patient is no longer inhaling. Inother words, it is assumed that no matter how shallow the breaths beingtaken are, the patient is still achieving a full exhalation. Shallowbreaths mean the patient is not achieving a full inhalation. Thus,images are shown at a regular interval until the patient begins toexhale. Then, the images are shown in reverse order at the exhalationinterval.

Algorithms and Experimental Results

Data Acquisition

An experiment was conducted that began with the acquisition of CT imagesof patients in two respiratory states: inhalation and exhalation. Adatabase of patients was divided into three categories according tobreathing amplitude (normal, moderate, extreme). Only patients withmoderate (full inhalation, normal exhalation) amplitude breathing wereused for the study.

For each patient about 200 pairs of points (landmarks) were marked onboth exhalation and inhalations CT images. The anatomical points weremarked on airway bifurcations or on blood vessels bifurcations for theperipheral areas where airway bifurcations were hardly to identify. Eachpair of matching points represents a breathing vector at that specificanatomic location. Landmark locations were chosen to be uniformlydistributed throughout the lung volume.

T:R ³ →R ³ TRANSFORMATION METHOD

Local tissue deformations can be learned by analyzing the displacementsof each landmark point. The missing data between the displacements ofeach landmark point can be interpolated.

Non-rigid registration techniques were used in order to get markedlandmark points to smoothly transform from one state to another. Themethods, functions and kernels are chosen according to the stability ofthe transformation and robustness to possible outliers. Thetransformation techniques used include polynomials, basis functions, andsplines.

Modeling can be performed for all landmarks to attain a global lungdeformation function that can be used for global calculations. It isalso possible to divide the lungs to smaller sub-parts that can bemodeled separately while simplifying the needed transformation. Forexample, analyzing the left and right sides of the lungs separatelyyielded good results.

The methods of the present invention allow describing lung tissuedeformations during breathing cycles using a low number of degrees offreedom with an acceptable level of inaccuracy. Hence, thetransformation can be produced or reproduced using a small number ofcontrol points (internal and/or external) with locations sampled in realtime.

The accuracy of the model is affected by the number of degrees offreedom of the transformation. However, over-fitting the model to thedata can make the model less robust. Approaching high transformationprecision values on the landmarks themselves (less then 1 mm) requiresthe use of complicated solutions that can behave poorly on the volumesbetween landmarks and are, therefore, less suitable for modeling.

Though an entire breathing vector set can be used as input data forfitting algorithm, the vectors may be divided according to anatomicalregions, such as left lung and right lung, for example.

Linear transformation models can be extended to non-lineartransformation models. For second order polynomial transformation:

${T( {x,y,z} )} = {\begin{pmatrix}x^{\prime} \\y^{\prime} \\z^{\prime} \\1\end{pmatrix} = {\begin{pmatrix}a_{00} & \Lambda & a_{08} & a_{09} \\a_{10} & \Lambda & a_{18} & a_{19} \\a_{20} & \Lambda & a_{28} & a_{29} \\0 & \Lambda & 0 & 1\end{pmatrix}\begin{pmatrix}x^{2} \\y^{2} \\M \\1\end{pmatrix}}}$

A polynomial fit is a specific type of linear multiple regression.

In order to build a polynomial transformation between the inhalation andexhalation breathing phases, the available pairs of points are used. Itis assumed that the points are distributed uniformly throughout thelungs and represent the global anatomical tissue displacement during therespiratory cycle.

Let U and V denote coordinates matrix of size 4×N for points of twostates, inhalation and exhalation respectively:

U=(

₁,

₂,. . . ,

_(N))

V=(

₁,

₂, . . . ,

_(N))

For N pairs of points:

$\begin{matrix}\begin{matrix}{V = \begin{pmatrix}x_{1}^{\prime} & x_{2}^{\prime} & \Lambda & x_{N}^{\prime} \\y_{1}^{\prime} & y_{2}^{\prime} & \Lambda & y_{N}^{\prime} \\z_{1}^{\prime} & z_{2}^{\prime} & \Lambda & z_{N}^{\prime} \\1 & 1 & \Lambda & 1\end{pmatrix}} \\{= {\begin{pmatrix}a_{00} & \Lambda & a_{08} & a_{09} \\a_{10} & \Lambda & a_{18} & a_{19} \\a_{20} & \Lambda & a_{28} & a_{29} \\0 & \Lambda & 0 & 1\end{pmatrix}\begin{pmatrix}x_{1}^{2} & x_{2}^{2} & \Lambda & x_{N}^{2} \\y_{1}^{2} & y_{2}^{2} & \Lambda & y_{N}^{2} \\M & M & \; & M \\1 & 1 & \Lambda & 1\end{pmatrix}}} \\{= {\Lambda \overset{\sim}{U}}}\end{matrix} & \; \\{where} & \; \\{\overset{\sim}{U} = {{f(U)} = ( {{f( {\overset{\rho}{u}}_{1} )},{f( {\overset{\rho}{u}}_{2} )},\ldots \mspace{14mu},{f( {\overset{\rho}{u}}_{N} )}} )}} & \;\end{matrix}$

is the function that transforms each column vector of U containing x, y,z to a column vector of higher dimension. In case of a second degreepolynomial, the 3D vector is transformed to 10D space by:

The minimum number of point pairs needed for identification of thetransformation is determined by the number of DOFs (degrees of freedom)for an output space of function ƒ. Thus, for a second degree polynomial,just 10 point pairs (or breathing vectors) are required. For a thirddegree polynomial, a minimum of 20 point pairs are requiredrespectively.

The mean error is calculated for all available points by:

$ɛ = {{A\overset{\sim}{U}} - V}$$m = {\frac{1}{N}{\sum\limits_{i}^{N}{ɛ_{i}}_{2}}}$

Deriving the Breathing Model

It is possible to calculate a polynomial transformation for eachavailable dataset (patient) given a sufficient number of matched pairsof points representing exhalation and inhalation states. In order toassess the similarity between breathing models for different patients,the 3D vector fields should be compared. Due to the inherent variabilityof different patients, it is difficult to apply a breathing model of onepatient directly to another patient. Nevertheless, there is anassumption that two breathing models can be matched together applyingsome simple transformation that can convert from one model to another:

T _(simple)(W)=S·g(W)

where the g( )transforms each vector to higher dimensional space and Sis the appropriate coefficient matrix.

In order to minimize the number of degrees of freedom, it is assumedthat the unknown transformation is a linear transformation (affine orperspective). Then the function g( ) performs the conversion intohomogeneous coordinates. Therefore S is of size 4×4.

When looking for simple transformation the cost function can be defined:

ε=A·ƒ(S·U)−S·V

$F = {\frac{1}{N}{\sum\limits_{i}^{N}{ɛ_{i}}_{2}}}$$S_{best} = {\underset{S_{4 \times 4}}{argmin}(F)}$

This optimization problem is solved using Nelder-Mead method or theSimplex Search method. The method uses the concept of a Simplex, whichis a polytope (generalization to any dimension of polygon) of N+1 vertexin N dimensions; a line segment on a line, a triangle on a plane, atetrahedron in three-dimensional space and so forth. The methodapproximately finds a locally optimal solution to a problem with Nvariables when the objective function varies smoothly.

The search for the global minimum is performed as a part of theoptimization task on the function F, defined above, in multi-dimensionalspace, which has 16 dimensions in this case.

The resulting S_(best) is used to fit the known polynomial function toother patient with undefined breathing model.

Grid Method

Assuming elastic properties of lung tissue, deformation at any givenpoint may be evaluated by close breathing vectors.

Initial breathing vectors were used for calculating new breathingvectors located at the nodes of 3D grid.

The described procedure was applied for 4 different patients after CTvolume normalization and registration. The final 3D vector field wasgenerated by averaging results of all patients.

For each grid vertex the integration is performed over defined volumespace around (using defined kernel function). The integration boundariescan be 3D cube of size N or sphere with radius N.

Anatomical Points Method

The respiratory motion can also be described by means of modeling the“skeletal” motion of the lungs. A skeletal tree of the lungs is producedby representing the bifurcations of the airways as nodes and thenconnecting the nodes to form a skeleton of the airways.

Skeletal trees are generated for two breathing states of the samepatient. Then the trees are combined together in order to identify thechanges that are modeled later by measuring the relative angles at thenodes.

Skeletal trees from different individuals can be further analyzed bycomparing the behavior of corresponding nodes from each patient.

The available data set has been divided to training and testing sets.The model parameters have been estimated by the training set andverified with the testing set proving the feasibility of the method.

Results

Transformation method: tissue deformations of the entire lung weremodeled using smooth vector function with an average fit error of about2 mm.

Grid method: 3 patients were used for building the model and 1 patientfor verification. After applying cross validation, the average error wasabout 4 mm.

Breathing vectors for patients with normal breathing intensity was 1-2mm in the central lung regions and 10-15 mm at the periphery(diaphragm).

Interpolation Results

The general breathing models that were obtained using the aforementionedtechnique were verified using cross-reference method. The model isderived from each of the available patients and then used for modelingbreathing for other available patients, including one used for modelgeneration in order to have a comparative lower limit error estimation.

Seven patients participated in the study. The following tables summarizethe mean errors and standard deviations when applying the breathingmodel derived from the patient on the row to each of the patients fromthe columns.

Mean Errors:

Patient1 Patient2 Patient3 Patient4 Patient5 Patient6 Patient7 Patient11.4441 30.3849 22.3949 9.579 6.7975 9.1251 17.5015 Patient2 8.04712.1803 26.975 7.3234 6.2768 6.2002 9.4439 Patient3 27.2102 31.89683.9853 12.5647 10.1514 18.2088 32.9139 Patient4 4.7568 5.1671 8.94723.4243 7.0903 5.7553 6.1695 Patient5 57.6078 22.6204 21.88 13.01423.6763 24.7327 41.5406 Patient6 31.4134 15.3444 51.4794 14.9238 13.79054.1377 27.2752 Patient7 19.0761 6.8696 8.2957 12.2098 6.9798 10.09022.403

Standard Deviation Values:

Patient1 Patient2 Patient3 Patient4 Patient5 Patient6 Patient7 Patient10.8592 12.2057 4.9473 4.4579 2.5962 5.4156 9.8278 Patient2 4.701 1.628313.9169 4.2816 3.4003 3.5902 7.437 Patient3 15.7571 17.4782 3.28236.9061 5.8878 12.9119 16.6467 Patient4 2.7333 3.9613 4.9235 2.321 3.17514.0883 4.2487 Patient5 3.8712 13.2514 9.6508 5.0819 2.6654 11.500216.0817 Patient6 9.4778 7.577 14.7764 9.0923 7.0307 2.7028 10.835Patient7 9.6453 5.2156 5.168 5.9022 4.2303 6.7865 1.3058

The italicized cells in the tables above determine the quality ofself-error, when the same patient used both for model derivation and forerror calculation. This number is expected to have the lowest value inthe row and column.

The existence of acceptable values of above-mentioned function F meansthat respiratory motion can be modeled by known polynomial function inconjunction with some linear transformation given by a 4×4 sized matrix.

As charted in FIG. 3, it is observed that in the above patient-relatedCT dataset, the best results are achieved when using the breathing modelgenerated from Patient4. The results of this polynomial approximationmethod can be compared to simple linear registration method using 7registration points.

Mean and standard deviation for errors after simple affine registrationusing 7 registration points:

Patient1 Patient2 Patient3 Patient4 Patient5 Patient6 Patient7 Mean10.4010 10.1197 11.9469 14.7198 14.5926 22.4039 14.7366 Std 7.29876.4501 7.5849 8.4310 8.6562 19.1004 10.0350

The above graph shows that approximation based on polynomialinterpolation achieves significantly more accurate results than regularrigid registration. Graphs showing the breathing error distributions foreach individual patient are provided as FIGS. 4-10:

Patient1: See FIGS. 4 a and 4 b.

Patient2: See FIGS. 5 a and 5 b.

Patient3: See FIGS. 6 a and 6 b.

Patient4: See FIGS. 7 a and 7 b.

Patient5: See FIGS. 8 a and 8 b.

Patient6: See FIGS. 9 a and 9 b.

Patient7: See FIGS. 10 a and 10 b.

It is drawn from the graphs in FIGS. 4-10 that breathing models obtainedusing the aforementioned technique were able to significantly reduce theerrors (or divergence) caused by inhalation\exhalation breathing statesdifference.

Generalization Analysis for Second Order Polynomial

It is proven that the generalization property has a significant effecton the registration error of volumes around the registration landmarkpoints.

The graph of FIG. 11 shows the comparison of registration error betweenrigid and polynomial-based transformations. Note that each value shownon the graph corresponds to the specific pair that did not participatein registration data set. This way the results are not biased by thetransformation. The FIG. 11 graph is based on left side lungregistration.

Compare the mean values of 8.3 mm after rigid registration to 3.2 mmafter polynomial based registration.

Degree of Polynomial

The mean registration errors are shown with confidence levels of twostandard deviations on the graph of FIG. 12. Note that both left andright lungs were used for registration.

The polynomial degree and element choice is determined by model accuracyspecifications.

CONCLUSIONS

Tissue deformations during the breathing cycle can be described using alow number of degrees of freedom with acceptable accuracy. Thetransformation can be reproduced using a small number of control points.

It is proven that a specific patient breathing motion can be modeledusing the preliminary constructed static “breathing pattern” matrix anda rigid transformation 4×4 matrix dynamically defined from the specificpatient.

The “breathing vectors” correction technique can be successfully usedduring electromagnetic bronchoscopy procedures to reduce localizationerrors. However, additional data sets are needed if method verificationis desired.

It is possible to reproduce the behavior of about 200 breathing vectorsby a reduced number of 20 vectors. When approximating the breathingmotion by a third order polynomial, 60 (20×3) degrees of freedom shouldbe determined. Hence, there is a system of 20 linear equations, whichmeans about 200 breathing vectors throughout the lungs can be reduced toa 3D vector field determined by just 20 vectors.

Using a simple linear transformation 4×4 in conjunction with a knownpreliminarily constructed constant 20×3 matrix, it is possible to modelthe breathing motion of a patient significantly, reducing theregistration error.

However, the ability of polynomials to recover anatomical shapevariability is often quite limited because they can model only global,not local, shape changes. Additionally, higher order polynomials tend tointroduce artifacts, such as oscillations. Therefore, the current methodmay be improved using other known techniques, such as B-Splines,Thin-Plate Splines, basis functions and others. Introduction ofadditional deformable component to current algorithm is expected toimprove the accuracy of the model. Using a weighting function may alsobe considered.

The other related issue deals with possible outlier removal. For examplethe outliers can be determined with regard to their correlation withregistration data set and filtered out. Such filtering is essential forbreathing motion generic model generation.

Non-uniform distribution of points is a problem that should be alsoaddressed during while modeling the breathing cycle. One possiblesolution is to use the same points several times in the data set inorder to assign them more weight in the algorithm.

There is a high variability of the breathing models generated fromdifferent patients by mean of the errors after performingcross-validation analysis. It is expected to find more patientsrepresenting “global breathing motion pattern” similar to Patient7 inthis study. Assuming the sufficiently accurate and compatible data setsthe fusion (or averaging) of several patients may be considered to getmore robust results.

It is concluded from the graphs that the error distributions areRayleigh distribution.

Although the invention has been described in terms of particularembodiments and applications, one of ordinary skill in the art, in lightof this teaching, can generate additional embodiments and modificationswithout departing from the spirit of or exceeding the scope of theclaimed invention. Accordingly, it is to be understood that the drawingsand descriptions herein are proffered by way of example to facilitatecomprehension of the invention and should not be construed to limit thescope thereof.

1-13. (canceled)
 14. A method of navigating a probe through airways ofthe lungs of a patient comprising: measuring patient characteristics;imaging said patient to acquire one or more images; identifying an areaof interest in the lungs of said patient; collecting data regardingpositions of key points on the patient's body while the patient isbreathing; developing a mathematical model of movement due to breathingusing said data; inserting a probe into said patient; displaying atleast one of said acquired images; displaying a real-time indication ofa position of said probe on said at least one of said acquired images;using said mathematical model to adjust relative positions of saidreal-time indication and said at least one acquired images such thatsaid real-time image is accurately portrayed on said at least oneacquired image.
 15. The method of claim 14 wherein measuring patientcharacteristics comprises taking measurements selected from the setconsisting of lung size, lung shape, lung health, altitude, patient age,diaphragm size, and diaphragm health.
 16. The method of claim 14 whereincollecting data regarding positions of key points on the patient's bodywhile the patient is breathing comprises collecting data from sensorsplaced on the patient.
 17. The method of claim 14 wherein developing amathematical model of movement due to breathing using said datacomprises creating a skeletal tree of the lungs and modeling theskeletal motion of the lungs.
 18. The method of claim 14 whereindeveloping a mathematical model of movement due to breathing using saiddata comprises: measuring movement due to breathing for at a pluralityof points in a plurality of patients; averaging the results of saidplurality of points in said plurality of patients; creating a3-dimensional vector field representative of average movements in thelungs; applying a vector corresponding to an area of interest in thelung to said at least one image in order to predict a location of saidarea of interest at a given point in the breathing cycle.
 19. The methodof claim 14 wherein developing a mathematical model of movement due tobreathing using said data comprises developing a mathematical algorithmthat models the lung movement of the patient.
 20. The method of claim 14wherein developing a mathematical model of movement due to breathingusing said data comprises calculating a polynomial transformation. 21.The method of claim 19 wherein developing a mathematical algorithm thatmodels the lung movement of the patient comprises collecting data on anumber of subjects in a study and relating movement of given locationsin said subjects to points in the respective breathing cycles of saidsubjects in which the positions were acquired.